Abstract
We have designed, synthesized, and evaluated using physical, chemical and biochemical assays various oligonucleotide N3'-->P5' phosphoramidates, as potential telomerase inhibitors. Among the prepared compounds were 2'-deoxy, 2'-hydroxy, 2'-methoxy, 2'-ribo-fluoro, and 2'-arabino-fluoro oligonucleotide phosphoramidates, as well as novel N3'-->P5' thio-phosphoramidates. The compounds demonstrated sequence specific and dose dependent activity with IC50 values in the sub-nM to pM concentration range.
MeSH terms
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Amides / chemical synthesis
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Amides / chemistry*
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Amides / pharmacology*
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology*
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Humans
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Inhibitory Concentration 50
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Oligonucleotides / chemical synthesis
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Oligonucleotides / chemistry*
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Oligonucleotides / pharmacology*
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Phosphoric Acids / chemical synthesis
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Phosphoric Acids / chemistry*
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Phosphoric Acids / pharmacology*
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Telomerase / antagonists & inhibitors*
Substances
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Amides
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Enzyme Inhibitors
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Oligonucleotides
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Phosphoric Acids
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phosphoramidic acid
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Telomerase